Identification

Neratinib was approved in July 2017 for use as an extended adjuvant therapy in Human Epidermal Growth Factor Receptor 2 (HER2) positive breast cancer. Approval was granted to Puma Biotechnology Inc. for the tradename Nerlynx. Neratinib is currently under investigation for use in many other forms of cancer.

Neratinib binds to and irreversibly inhibits EGFR, HER2, and HER4 [FDA Label]. This prevents auotphoshorylation of tyrosine residues on the receptor and reduces oncogenic signalling through the mitogen-activated protein kinase and Akt pathways.

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

Neratinib and its major active metabolites M3. M6, and M7 have a Tmax of 2-8 h [FDA Label]. Administration with a high fat meal increases Cmax by 1.7-fold and total exposure by 2.2-fold. Administration with a standard meal increases Cmax by 1.2-fold and total exposure by 1.1-fold. Administration with gastric acid reducing agents such as proton pump inhibitors reduces Cmax by 71% and total exposure by 65%.

Volume of distribution

The apparent volume of distribution at steady state is 6433 L [FDA Label].

Neratinib is mainly undergoes metabolism via CYP3A4 [FDA Label]. It is also metabolized by flavin-containing monooxygenase to a lesser extent. The systemic exposures of neratinib's active metabolites M3, M6, M7, and M11 are 15%, 33%, 22%, and 4%.

Route of elimination

97.1% of the total dose is excreted in the feces and 1.13% in the urine [FDA Label].

Half life

The mean half life of elimination ranges from 7-17 h following a single dose [FDA Label]. The mean plasma half life during multiple doses is 14.6 h for neratinib, 21.6 h for M3, 13.8 h for M6, and 10.4 h for M7.

Clearance

The total clearance during multiple doses is 216 L/h for after the first dose and 281 L/h during steady state [FDA Label].